-
Parasites & Vectors May 2018Leishmaniasis is a vector-borne disease caused by many Leishmania species, which can infect both humans and other mammals. Leishmaniasis is a complex disease, with... (Review)
Review
Leishmaniasis is a vector-borne disease caused by many Leishmania species, which can infect both humans and other mammals. Leishmaniasis is a complex disease, with heterogeneous clinical manifestations ranging from asymptomatic infections to lesions at cutaneous sites (cutaneous leishmaniasis), mucosal sites (mucocutaneous leishmaniasis) or in visceral organs (visceral leishmaniasis), depending on the species and host characteristics. Often, symptoms are inconclusive and leishmaniasis can be confused with other co-endemic diseases. Moreover, co-infections (mainly with HIV in humans) can produce atypical clinical presentations. A correct diagnosis is crucial to apply the appropriate treatment and the use of molecular techniques in diagnosis of leishmaniasis has become increasingly relevant due to their remarkable sensitivity, specificity and possible application to a variety of clinical samples. Among them, real-time PCR (qPCR)-based approaches have become increasingly popular in the last years not only for detection and quantification of Leishmania species but also for species identification. However, despite qPCR-based methods having proven to be very effective in the diagnosis of leishmaniasis, a standardized method does not exist. This review summarizes the qPCR-based methods in the diagnosis of leishmaniasis focusing on the recent developments and applications in this field.
Topics: Animals; Humans; Leishmania; Leishmaniasis; Molecular Diagnostic Techniques; Parasitology; Real-Time Polymerase Chain Reaction
PubMed: 29716641
DOI: 10.1186/s13071-018-2859-8 -
Parasites & Vectors Feb 2017In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical... (Review)
Review
In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20 century and the discovery of new Leishmania and sand fly species continued well into the 21 century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic.
Topics: Animals; Fossils; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Leishmania; Leishmaniasis
PubMed: 28202044
DOI: 10.1186/s13071-017-2028-5 -
Expert Review of Proteomics May 2018Leishmania spp. are causative agents of leishmaniasis, a broad-spectrum neglected vector-borne disease. Genomic and transcriptional studies are not capable of solving... (Review)
Review
Leishmania spp. are causative agents of leishmaniasis, a broad-spectrum neglected vector-borne disease. Genomic and transcriptional studies are not capable of solving intricate biological mysteries, leading to the emergence of proteomics, which can provide insights into the field of parasite biology and its interactions with the host. Areas covered: The combination of genomics and informatics with high throughput proteomics may improve our understanding of parasite biology and pathogenesis. This review analyses the roles of diverse proteomic technologies that facilitate our understanding of global protein profiles and definition of parasite development, survival, virulence and drug resistance mechanisms for disease intervention. Additionally, recent innovations in proteomics have provided insights concerning the drawbacks associated with conventional chemotherapeutic approaches and Leishmania biology, host-parasite interactions and the development of new therapeutic approaches. Expert commentary: With progressive breakthroughs in the foreseeable future, proteome profiles could provide target molecules for vaccine development and therapeutic intervention. Furthermore, proteomics, in combination with genomics and informatics, could facilitate the elimination of several diseases. Taken together, this review provides an outlook on developments in Leishmania proteomics and their clinical implications.
Topics: Animals; Humans; Leishmania; Parasites; Proteome; Proteomics; Protozoan Proteins; Systems Biology
PubMed: 29717934
DOI: 10.1080/14789450.2018.1468754 -
Parasite (Paris, France) 2019Leishmaniases still represent a global scourge and new therapeutic tools are necessary to replace the current expensive, difficult to administer treatments that induce... (Review)
Review
Leishmaniases still represent a global scourge and new therapeutic tools are necessary to replace the current expensive, difficult to administer treatments that induce numerous adverse effects and for which resistance is increasingly worrying. In this context, the particularly original organization of the Leishmania parasite in comparison to higher eukaryotes is a great advantage. It allows for the development of new, very specific, and thus non-cytotoxic treatments. Among these originalities, Leishmania cell death can be cited. Despite a classic pattern of apoptosis, key mammalian apoptotic proteins are not present in Leishmania, such as caspases, cell death receptors, and anti-apoptotic molecules. Recent studies have helped to develop a better understanding of parasite cell death, identifying new proteins or even new apoptotic pathways. This review provides an overview of the current knowledge on Leishmania cell death, describing its physiological roles and its phenotype, and discusses the involvement of various proteins: endonuclease G, metacaspase, aquaporin Li-BH3AQP, calpains, cysteine proteinase C, LmjHYD36 and Lmj.22.0600. From these data, potential apoptotic pathways are suggested. This review also offers tools to identify new Leishmania cell death effectors. Lastly, different approaches to use this knowledge for the development of new therapeutic tools are suggested: either inhibition of Leishmania cell death or activation of cell death for instance by treating cells with proteins or peptides involved in parasite death fused to a cell permeant peptide or encapsulated into a lipidic vector to target intra-macrophagic Leishmania cells.
Topics: Animals; Apoptosis; Cell Death; Humans; Leishmania; Leishmaniasis; Metabolic Networks and Pathways; Phenotype; Psychodidae
PubMed: 31825305
DOI: 10.1051/parasite/2019071 -
Frontiers in Cellular and Infection... 2022The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor...
The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by subgenus showing infectious metastasis and resulting in severe distant secondary lesions, the route of escape of these parasites to secondary sites has not yet been investigated in detail. Our results demonstrated that when infection was associated with inflammation and additionally exacerbated by the presence of dsRNA viral endosymbiont (LRV1), lymphatic vessels could serve as efficient routes for infected cells to egress from the primary site and colonize distant organs. We challenged this hypothesis by using the intracellular protozoan parasites associated with or without a dsRNA viral endosymbiont, exacerbating the infection and responsible for a strong inflammatory response, and favoring metastasis of the infection. We analyzed possible cargo cells and the routes of dissemination through flow cytometry, histological analysis, and imaging in our metastatic model to show that parasites disseminated not only intracellularly but also as free extracellular parasites using migrating immune cells, lymph nodes (LNs), and lymph vessels, and followed intricate connections of draining and non-draining lymph node to finally end up in the blood and in distant skin, causing new lesions.
Topics: Humans; Leishmania; Leishmania braziliensis; Leishmaniasis, Mucocutaneous; Lymphatic System; Neoplasms
PubMed: 36034709
DOI: 10.3389/fcimb.2022.941860 -
G3 (Bethesda, Md.) Jan 2022Insufficient and irregular data reports on Leishmaniasis, issuing from the developing world, have left much to be desired in terms of understanding the molecular...
Insufficient and irregular data reports on Leishmaniasis, issuing from the developing world, have left much to be desired in terms of understanding the molecular signatures producing distinct infectious phenotypes of the disease. Herein, we report on the complete genome sequencing of Leishmania naiffi and Leishmania guyanensis, sampled from patients in regions of Colombia and Venezuela. In this study, the isolates of cutaneous lesions from both species presented limited structural variation at the chromosomal level, low gene copy number variation, and high genetic heterogeneity. We compared these sequences to the reference genomes hitherto related from Brazil and French Guyana. Although of the same species, we note a consequential genomic disparity between the Venezuelan and French Guyanese isolates of L. guyanensis. Although less significant on the global schema of cutaneous and mucosal disease, such genomic studies of L. naiffi and L. guyanensis substantiate the gaps in understanding of the molecular architecture and multivariate clinical pictures of Leishmaniasis, on an international scale.
Topics: DNA Copy Number Variations; Genomics; Humans; Leishmania; Leishmania guyanensis; Skin
PubMed: 34791158
DOI: 10.1093/g3journal/jkab377 -
Molecular and Biochemical Parasitology Apr 2010In many eukaryotes, phospholipids (PLs) and sphingolipids (SLs) are abundant membrane components and reservoirs for important signaling molecules. In Leishmania, the... (Review)
Review
In many eukaryotes, phospholipids (PLs) and sphingolipids (SLs) are abundant membrane components and reservoirs for important signaling molecules. In Leishmania, the composition, metabolism, and function of PLs and SLs differ significantly from those in mammalian cells. Although only a handful of enzymes have been experimentally characterized, available data suggest many steps of PL/SL metabolism are critical for Leishmania viability and/or virulence, and could be a source for new drug targets. Further studies of genes involved in the synthesis (de novo and salvage) and degradation of PLs and SLs will reveal their diverse effects on Leishmania pathogenesis.
Topics: Animals; Biosynthetic Pathways; Leishmania; Phospholipids; Sphingolipids
PubMed: 20026359
DOI: 10.1016/j.molbiopara.2009.12.004 -
Seminars in Cell & Developmental Biology May 2011Methylglyoxal is a toxic by-product of glycolysis and other metabolic pathways. In mammalian cells, the principal route for detoxification of this reactive metabolite is... (Review)
Review
Methylglyoxal is a toxic by-product of glycolysis and other metabolic pathways. In mammalian cells, the principal route for detoxification of this reactive metabolite is via the glutathione-dependent glyoxalase pathway forming d-lactate, involving lactoylglutathione lyase (GLO1; EC 4.4.1.5) and hydroxyacylglutathione hydrolase (GLO2; EC 3.2.1.6). In contrast, the equivalent enzymes in the trypanosomatid parasites Trypanosoma cruzi and Leishmania spp. show >200-fold selectivity for glutathionylspermidine and trypanothione over glutathione and are therefore sensu stricto lactoylglutathionylspermidine lyases (EC 4.4.1.-) and hydroxyacylglutathionylspermidine hydrolases (EC 3.2.1.-). The unique substrate specificity of the parasite glyoxalase enzymes can be directly attributed to their unusual active site architecture. The African trypanosome differs from these parasites in that it lacks GLO1 and converts methylglyoxal to l-lactate rather than d-lactate. Since Trypanosoma brucei is the most sensitive of the trypanosomatids to methylglyoxal toxicity, the absence of a complete and functional glyoxalase pathway in these parasites is perplexing. Alternative routes of methylglyoxal detoxification in T. brucei are discussed along with the potential of exploiting trypanosomatid glyoxalase enzymes as targets for anti-parasitic chemotherapy.
Topics: Animals; Antiprotozoal Agents; Humans; Lactoylglutathione Lyase; Leishmania; Pyruvaldehyde; Thiolester Hydrolases; Trypanosoma
PubMed: 21310261
DOI: 10.1016/j.semcdb.2011.02.001 -
Current Opinion in Microbiology Dec 2013Iron is essential for many metabolic pathways, but is toxic in excess. Recent identification of the ferric iron reductase LFR1, the ferrous iron transporter LIT1, and... (Review)
Review
Iron is essential for many metabolic pathways, but is toxic in excess. Recent identification of the ferric iron reductase LFR1, the ferrous iron transporter LIT1, and the heme transporter LHR1 greatly advanced our understanding of how Leishmania parasites acquire iron and regulate its uptake. LFR1 and LIT1 have close orthologs in plants, and are required for Leishmania virulence. Consistent with the lack of heme biosynthesis in trypanosomatids, LHR1 and LABCG5, a protein involved in heme salvage from hemoglobin, seem essential for Leishmania survival. LFR1, LIT1 and LHR1 are upregulated under low iron availability, in agreement with the need to prevent excessive iron uptake. Future studies should clarify how Leishmania interacts with the iron homeostasis machinery of its host cell, the macrophage.
Topics: Homeostasis; Iron; Leishmania; Metabolic Networks and Pathways
PubMed: 23962817
DOI: 10.1016/j.mib.2013.07.018 -
Medical Sciences (Basel, Switzerland) Apr 2022Parasites of the genus cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is... (Review)
Review
Parasites of the genus cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in . Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host-parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, -adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against parasites.
Topics: Animals; Leishmania; Ornithine Decarboxylase; Parasites; Polyamines; Spermidine Synthase
PubMed: 35645240
DOI: 10.3390/medsci10020024